Recombinant YopE and LcrV vaccine candidates protect mice against plague and yersiniosis.

No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of Yersinia pestis was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1ß from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD50Y. pestis infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with Yersinia pseudotuberculosis and Yersinia enterocolitica. Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against Yersinia infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. However, the efficacy should be tested in other higher mammalian models.

Antibiotic resistance: a global crisis, problems and solutions.

Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has increased in pathogenic microbes. World Health Organization (WHO) has announced ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) as the top priority pathogens as these have developed resistance against certain antibiotics. To combat such a global issue, it is utmost important to identify novel therapeutic strategies/agents as an alternate to such antibiotics. To name certain antibiotic adjuvants including: inhibitors of beta-lactamase, efflux pumps and permeabilizers for outer membrane can potentially solve the antibiotic resistance problems. In this regard, inhibitors of lytic domain of lytic transglycosylases provide a novel way to not only act as an alternate to antibiotics but also capable of restoring the efficiency of previously resistant antibiotics. Further, use of bacteriophages is another promising strategy to deal with antibiotic resistant pathogens. Taking in consideration the alternatives of antibiotics, a green synthesis nanoparticle-based therapy exemplifies a good option to combat microbial resistance. As horizontal gene transfer (HGT) in bacteria facilitates the evolution of new resistance strains, therefore identifying the mechanism of resistance and development of inhibitors against it can be a novel approach to combat such problems. In our perspective, host-directed therapy (HDT) represents another promising strategy in combating antimicrobial resistance (AMR). This approach involves targeting specific factors within host cells that pathogens rely on for their survival, either through replication or persistence. As many new drugs are under clinical trials it is advisable that more clinical data and antimicrobial stewardship programs should be conducted to fully assess the clinical efficacy and safety of new therapeutic agents.

Chitosan and neem gum-based polyelectrolyte complex for design of allantoin loaded biocomposite film: In-vitro, ex-vivo, and in-vivo characterization.

Presently, the preference for chitosan (CS) and gum polysaccharides in biomedical applications including drug delivery and wound healing has been extensively documented. Despite this, the demerits of CS and gum polysaccharides such as poor mechanical properties, degradation rate, swelling, etc., limit their applications for designing biocomposite films for drug delivery. Therefore, the anticipated work aims to design a CS and neem gum polysaccharides (NGP) polyelectrolyte complex-based allantoin (AT)-loaded (CS/NGP-AT) biocomposite film for improved wound healing. In brief, CS, NGP, and CS/NGP-AT-based biocomposite films were prepared using the solvent-casting method, and in-vitro, ex-vivo, and in-vivo characterizations were performed to assess the performance of these biocomposite films compared to their counterparts. In this, diffractogram and thermogram analysis assured the conversion of crystalline AT into an amorphous form. The optimized CS/NGP/AT-3 formulation exhibited controlled water absorption, appropriate water uptake capacity, good water retention ability, excellent water vapor transmission rate, controlled degradation rate, enhanced mechanical properties, cell and blood biocompatibility, etc. Furthermore, it offered improved antimicrobial, anti-inflammatory, and antioxidant potential. The optimized film provided a modified release (88.3 ± 0.3 %) of AT from the film for up to 48 h. Wound healing experiments on rats and their histopathology studies confirmed a significantly higher rate of wound recovery within 14 days compared to the control and CS/NGP film, attributable to the combined effects of CS, NGP, and AT. In conclusion, the fabricated CS/NGP-based biocomposite film presents promising prospects as an excellent candidate for wound healing applications.

Degradation of Diazo Dye and its Kinetic and Equilibrium Studies Using the Potential of Bryophyllum fedtschenkoiin Aqueous System.

Phytoremediation is emerging as an eco-friendly, innovative, and cost-effective approach for the removal of textile dyes from wastewater from the previous decade. The current research work aims to explore the potential of a terrestrial ornamental plant, Bryophyllum fedtschenkoi (Raym.-Hamet & H. Perrier) Lauz.-March. for remediating the diazo dye as Congo red (CR) in aqueous form. B. fedtschenkoi was grown hydroponically before treatment with 100 mL of a different concentration of CR dye solution. A maximum decolorization potential of 90% was obtained for 10 mg L- 1 after 40 h of equilibrium. The kinetic studies have revealed that the experimental results for the removal of CR dye using the B .fedtschenkoi plant are suitable for Pseudo-first order with R2 ≥ 0.92, while the equilibrium studies agreed with the Freundlich adsorption isotherm with R2 ≥ 0.909. The dye removal by the plant was confirmed with the help of analytical techniques Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) were also performed on dye-degraded metabolites to explore the mechanism of dye degradation.

Rapid detection of carbapenem resistance among gram-negative organisms directly from positive blood culture bottles.

Background: Carbapenemase producing gram-negative bacteria (GNB) has become a huge problem in majority of tertiary care centers worldwide. They are associated with very high morbidity and mortality rates, especially when they cause invasive infections. Therefore, rapid detection of these organisms is very important for prompt and adequate antibiotic therapy as well as infection control. The aim of this study was rapid detection of carbapenemase genes and thereby likely carbapenem resistance, 24-48 hours in advance, directly from the positive-flagged blood culture bottles using CHROMagar and Xpert® Carba-R. Methods: Aspirate from positively flagged blood culture bottles was subjected to differential centrifuge. All gram-negative bacilli on gram stain from the deposit were processed in Xpert® Carba-R and inoculated on CHROMagar. The presence of genes and growth on CHROMagar was compared with carbapenem resistance on VITEK-2 Compact. Results: A total of 119 GNB isolates were processed. One or more of the carbapenemase genes were detected in 80 isolates. On comparison with VITEK-2 result, 92 samples showed concordance for carbapenem resistance 48 hours in advance. There was discordance in 21 isolates with 12 major errors and 09 minor errors. The sensitivity of direct Xpert® Carba-R test for rapid detection of carbapenem resistance, 48 hours in advance, was 81.42%. The sensitivity of direct CHROMagar test for accurate detection of carbapenem resistance, 24 hours in advance, was 92.06%. Conclusion: The ability to detect carbapenem resistance with very high accuracy, 48 hours in advance, helps in appropriate antibiotic therapy and implementation of effective infection control practices.

New-age vaccine adjuvants, their development, and future perspective.

In the present scenario, immunization is of utmost importance as it keeps us safe and protects us from infectious agents. Despite the great success in the field of vaccinology, there is a need to not only develop safe and ideal vaccines to fight deadly infections but also improve the quality of existing vaccines in terms of partial or inconsistent protection. Generally, subunit vaccines are known to be safe in nature, but they are mostly found to be incapable of generating the optimum immune response. Hence, there is a great possibility of improving the potential of a vaccine in formulation with novel adjuvants, which can effectively impart superior immunity. The vaccine(s) in formulation with novel adjuvants may also be helpful in fighting pathogens of high antigenic diversity. However, due to the limitations of safety and toxicity, very few human-compatible adjuvants have been approved. In this review, we mainly focus on the need for new and improved vaccines; the definition of and the need for adjuvants; the characteristics and mechanisms of human-compatible adjuvants; the current status of vaccine adjuvants, mucosal vaccine adjuvants, and adjuvants in clinical development; and future directions.

Safety and outcome of ultrasound-guided tunneled central venous catheter in children with cancers from low middle-income country: A prospective study.

BACKGROUND: Central venous access devices (CVAD) are vital for cancer therapeutics in pediatric oncology. Tunneled vascular access devices (TVAD) are preferred in children for prolonged and frequent vascular access. Data on insertion, care, and complications of CVAD in children from low middle-income countries (LMIC) are scarce, heterogeneous, and retrospective. PROCEDURE: This prospective observational study on eligible children <12 years with pediatric malignancies requiring chemotherapy for minimum 6 months from diagnosis excluded children with mucosal bleeding, coagulopathy, and infections. TVAD insertion was ultrasound (USG) guided. Number of catheter-days, surgical and nonsurgical complications, and risk factors for catheter-related bloodstream infections (CRBSI) were noted TVAD removal due to complications, therapy completion, tumor progression, or death. RESULTS: Data from 61 of 86 eligible children with median age 42 months (range 1-144) were analyzed. Hematological malignancy and severe thrombocytopenia were seen in 37/61 (61%) and 18/61 (30%) children, respectively. First-attempt success rate was 74%. Surgical complications were seen in four of 61 (7%). Nonsurgical complications were seen in 33/61 (54%) children; CRBSI was commonest 24/61 (39%), causing removal of TVAD in 14/61 (23%). Incidence per 1000 catheter-days for CRBSI was 3.24. Antibiotic lock therapy could salvage nine of 24 TVAD with CRBSI. Thrombus and accidental removal was seen in six of 61 (10%) and four of 61 (7%). None of the studied risk factors were significantly associated with CRBSI. The mean insertion duration of TVAD was 121 ± 90 days. CONCLUSION: USG-guided TVAD insertion is safe and reliable way for chemotherapy administration with acceptable complications in children with malignancies in LMIC, including children with severe thrombocytopenia.

Kinetic Evaluation for Removal of an Anionic Diazo Direct Red 28 by Using Phytoremediation Potential of Salvinia molesta Mitchell.

The dye removal using phytoremediation has demonstrated its potential to degrade many recalcitrant dyes. The kinetic investigations for phytoremediation ability of Salvinia molesta Mitchell (S. molesta) were evaluated for Direct Red 28 (DR28) dye in the present research work. The potential of S. molesta was analysed at different pH and different initial dye concentrations. About 90 % of dye decolorization was achieved for 50 mg L-1 dye solution with 4 g of S. molesta plant at pH 6.5. The experimental results were evaluated with pseudo-first, pseudo-second and Elovich kinetic models. The validation indicated the most suitable curve with Pseudo-second order having the correlation value R2 ≥ 0.99. FTIR studies supported the phytoextraction of DR28 through functional group interaction between plant hairy roots and dye molecules. The results of the present studies suggests that S. molesta can be utilized for remediation of water bodies and wetlands contaminated with dye wastewater in natural conditions.

A review on application of phytoremediation technique for eradication of synthetic dyes by using ornamental plants.

Phytoremediation emerges as an innovative and eco-friendly technique to remediate textile dyes with the use of various categories of plants. In recent years, ornamental plants emerge as more attractive and effective substitute in comparison to edible plants for phytoremediation. Regardless of aesthetic value, some ornamental plants can be grown to remediate the sites contaminated with dyes, heavy metals, pesticides, or other organic compounds. In this review, we focus on pioneer research on synthetic dye removal using ornamental plants and evaluate the phytoremediation capability of ornamental plants for treatment of textile effluent. This paper also emphasized specific ornamental plants having high accumulation and tolerance ability for removal of dyes. The mechanisms explored for the phytoremediation of dyes by ornamental plants have also been explained. This review will also be helpful for researchers for exploring more new ornamental plants in phytoremediation technique.

Advanced strategies for development of vaccines against human bacterial pathogens.

Infectious diseases are one of the main grounds of death and disabilities in human beings globally. Lack of effective treatment and immunization for many deadly infectious diseases and emerging drug resistance in pathogens underlines the need to either develop new vaccines or sufficiently improve the effectiveness of currently available drugs and vaccines. In this review, we discuss the application of advanced tools like bioinformatics, genomics, proteomics and associated techniques for a rational vaccine design.

Asia's largest urban slum-Dharavi: A global model for management of COVID-19.

The Dharavi sector of Mumbai, India is constituted as one of the biggest slums of Asia and the world's most populated areas. The COVID-19 outburst is at its peak in May and curve gets flattened within next two months. This article focuses on factors responsible for transmission, prevention and in controlling the COVID-19 spread in Dharavi. The COVID-19 data was interpreted in terms of Case Recovery Rate (CRR) and Case Fatality Rate (CFR) for total and closed both. The CFR per closed reached 10.12% nearly to per total 9.82% in Dharavi on 31st July 2020. The CRR per total cases in Dharavi and Mumbai is 87.16 & 76.18% and per closed cases is 89.87 & 93.20% respectively in comparison to the CFR. The calculated CFR and CRR for both Dharavi and Mumbai suggest that the COVID-19 recovery rate is more than the fatality rate. The Dharavi people serve as an important role in controlling the pandemic by adopting 4-T model tracing, tracking, testing, and treating strategy. This article is beneficial for government policy makers and private agencies in controlling the COVID-19 pandemic in densely populated areas and also for nations with high fatality rate.

A critical review on recent developments in MOF adsorbents for the elimination of toxic heavy metals from aqueous solutions.

Effective and substantial remediation of contaminants especially heavy metals from water is still a big challenge in terms of both environmental and biological perspectives because of their adverse effects on the human health. Many techniques including adsorption, ion exchange, co-precipitation, chemical reduction, ultrafiltration, etc. are reported for eliminating heavy metal ions from the water. However, adsorption has preferred because of its simple and easy handlings. Several types of adsorbents are observed and documented well for the purpose. Recently, highly porous metal-organic frameworks (MOFs) were developed by incorporating metals and organic ligands together and claimed as potent adsorbents for the remediation of highly toxic heavy metals from the aqueous solutions due to their unique features like greater surface area, high chemical stability, green and reuse material, etc. In this review, the authors discussed systematically some recent developments about secure MOFs to eliminate the toxic metals such as arsenic (both arsenite and arsenate), chromium(VI), cadmium (Cd), mercury (Hg) and lead (Pb). MOFs are observed as the most efficient adsorbents with greater selectivity as well as high adsorption capacity for metallic contamination. Graphical abstract.

Epidemic Trend of COVID-19 Transmission in India During Lockdown-1 Phase.

To assess the current epidemic trend of COVID-19/SARS-CoV-2 in India, the epidemic dynamics of COVID-19 cases in India in terms of Case Fatality Rate (CFR), Case Recovery Rate (CRR) and Mortality rate (MR) COVID-19 have been evaluated during Lockdown-1. The analysis includes (i) epidemic curve of Covid-19 cases (ii) demographic analysis (iii) calculation of the CFR and CRR by different methods (iv) calculation of MR (v) Geo-temporal analysis (vi) epidemiological transmission factor (vii) evaluation of the effects and impact of infection, prevention and control in India. A total of 10,815 COVID-19 confirmed cases have been reported in 31 states/union territories as of April 14, 2020 with 9272 active cases (85.73%), 1190 cured/discharged (11%), and 353 deaths (3.23%). Among confirmed cases, most cases (59%) are aged 20-49 which is working age in India and 76% cases are reported for men. The median age of Indian COVID-19 patients found to be 39. As of April 14, the CFR per total cases in India is 3.32% and per closed cases is 23.27%. The CRR per total cases in India is 11.00% and per closed cases is 76.72%, which indicates that the recovery rate of COVID-19 is more than the fatality rate in India. The prevention and control measures taken by the state and central governments at all levels and measure of maintenance of social distancing by people have resulted in effective curbing in the COVID-19 transmission in India.

Phytoremediation of azo dye methyl red by macroalgae Chara vulgaris L.: kinetic and equilibrium studies.

Phytoremediation is an innovative, eco-friendly, and solar-driven technique, which becomes a well-known alternative solution for remediation of hazardous dyes from wastewater. In present research work, potential of a submerged fresh water macroalgae Chara vulgaris L. (C. vulgaris) examined for removal of acidic azo dye methyl red (MR) in its solution form. A series of experiments were done with C. vulgaris to predict the effects of different parameters viz. contact time, initial dye concentration, amount of macroalgae, and pH. The increase in initial dye concentration directly impacts on the potential of macroalgae. The decolorization percentage declined with increase in initial dye concentration. The equilibrium condition was found to achieve after contact time of approximately 48 h. The decolorization of MR dye was found to be favorable at pH 5. The macroalgae was successfully utilized repeatedly with MR for eight cycles in batch experiments. The kinetics of phytoremediation of MR dye was studied with help of pseudo-first-order, pseudo-second-order, and Elovich kinetic models and the results were well suited to pseudo-second-order kinetic model with the correlation value R2 ≥ 0.99. In addition, the experimental data was also assessed by using Langmuir and Freundlich adsorption equilibrium isotherms. The results of phytoremediation data was found to be in favor of Freundlich equilibrium isotherm which having the correlation value R2 ≥ 0.977. The intraparticle diffusion model also studied to interpret the macroalgae phytoremediation mechanism for phytoremediation of MR. The surface interactions of C. vulgaris were investigated before and after the removal of dye with Fourier transform-infrared spectroscopy (FTIR) technique. On the basis of these studies, a hypothetical mechanism has also been proposed to depict the phytoremediation of acidic azo dye by C. vulgaris.

Assessment of Phytoremediation Potential of Chara vulgaris to Treat Toxic Pollutants of Textile Effluent.

Textile effluent released into water bodies is prone to be toxic for aquatic flora and fauna. In the present study, the phytoremediation potential of Chara vulgaris (C. vulgaris) is investigated for treatment of textile effluent. The highly concentrated and toxic textile effluent is diluted to different concentrations 10%, 25%, 50%, and 75% to check the accessibility of macroalgae to bear pollutant load of textile effluent. The toxicity of textile effluent is analysed by determining different water quality parameters, namely, pH, TDS, BOD, COD, and EC. The maximum reductions in TDS (68%), COD (78%), BOD (82%), and EC (86%) were found in the 10% concentrated textile effluent after 120 h of treatment. The highly concentrated textile effluent showed its toxic effect on macroalgae and it was found unable to show a remarkable change in water quality parameters of 75% and 100% textile effluent. The correlation coefficient values are determined using correlation matrix to identify the high correlation between different water quality parameters. The removal of toxic organic pollutants by C. vulgaris was confirmed by using UV-visible absorption spectra. Typical X-ray spectra recorded using EDXRF technique indicated the presence of heavy metals Cd in the dried sample of macroalgae after treatment which show its capability to remove toxic heavy metals from textile effluent. The reliability model has been proposed for treated textile effluents to identify percentage level of toxicity tolerance of waste water by macroalgae.

Role of Phytoremediation in Reducing Cadmium Toxicity in Soil and Water.

Heavy metals are a noxious form of pollutants present in soil and water. A new plant-based solar energy driven technology, phytoremediation, emerges as eco-friendly and cost-effective approach to remove heavy metal from various media with the help of hyperaccumulating plant species. This review paper aims to provide information on phytoremediation and its mechanisms for heavy metal removal especially to focus on Cadmium (Cd) metal and highlights the role of various hyperaccumulating plants for Cd metal remediation in soil and water. It complies various field case studies which play the important role in understanding the Cd removal through various plants. Additionally, it pinpoints several sources and the effects of Cd and other technologies used for Cd remediation. This paper provides the recent development in mechanisms of Cd hyperaccumulation by different plants, in order to motivate further research in this field.

US food and drug administration Indian site inspections: An experience.

Since 2005, USFDA has begun inspections of Indian clinical trial investigator sites. This paper reports experience of an FDA inspection performed at two Indian centers. The inspection started with an in-depth discussion with the investigator and his team about the conduct of the clinical trial at the site and was followed by a tour of the important locations - registration, outpatient department, specialty clinic, medical record section, and special procedure department. The inspector reviewed the critical processes - protocol compliance, ethics committee approval, informed consent process, case record form and source documents completion, investigational product accountability, serious adverse events documentation and reporting. The inspector reviewed all documents from the investigator site file and conducted audit of all subjects enrolled at both the sites. As the Indian sites are not exposed to regulatory inspections, it is vital for the sponsor to conduct preinspection audit, provide training and support to face the FDA inspection.

Transmetallation and gadolinium: do low iron stores prevent the development of nephrogenic systemic fibrosis in high-risk end-stage renal disease patients?

Nephrogenic systemic fibrosis (NSF) is a systemic disorder that occurs in patients with renal failure and manifests as a thickening of the skin and flexion contractures of the joints. The etiology may involve an exposure to a gadolinium (Gd)-based magnetic resonance contrast agent. It has been proposed that in hemodialysis (HD) patients, iron mobilization (decreased total iron-binding capacity, increased iron level, and transferrin oversaturation) causes a transmetallation reaction and the release of free Gd from its chelator with the deposition of both Gd and iron in the affected tissues leading to fibrosis. The objective of this study was to investigate whether the use of gadopentetate dimeglumine leads to iron mobilization and to the development of NSF in HD patients. A retrospective chart analysis of 236 HD patients was performed and patients who had received a Gd-containing contrast agent were selected for analysis of their iron studies before and after the Gd exposure. A total of 25 patients were identified as having had a magnetic resonance imaging study and all were administered gadopentetate dimeglumine and no patients had any signs or symptoms suggestive of NSF. Six patients had the appropriate iron studies, which showed no statistically significant difference in the serum iron, total iron-binding capacity, ferritin, or transferrin saturation before and after exposure to gadopentetate dimeglumine. Our data suggest that the use of gadopentetate dimeglumine in HD patients did not cause iron mobilization and transmetallation therefore may partially explain the lack of development of NSF seen in our patient population.